JP2020537514A5

JP2020537514A5 -

Info

Publication number: JP2020537514A5
Application number: JP2020518706A
Authority: JP
Filing date: 2018-10-01
Publication date: 2021-11-11

Description

本発明は、表１または５に言及されるいずれかの遺伝子座、遺伝子または領域での染色体相互作用の検出を含む。本発明は、染色体相互作用を検出するための本明細書に記載の核酸およびプローブの使用、例えば、少なくとも１、２、４、６または８の異なる遺伝子座または遺伝子における染色体相互作用を検出するための少なくとも１、２、４、６または８のそのような核酸またはプローブの使用を含む。本発明は、表２または７に挙げられるいずれかのプライマーまたはプライマーペアを使用する、または本明細書に記載のこれらのプライマーの変異体を使用する染色体相互作用の検出を含む（プライマー配列を含むまたはプライマー配列のフラグメントおよび／またはホモログを含む配列）。 The present invention includes the detection of chromosomal interactions at any of the loci, genes or regions referred to in Table 1 or 5. The present invention uses the nucleic acids and probes described herein to detect chromosomal interactions, eg, to detect chromosomal interactions at at least 1, 2, 4, 6 or 8 different loci or genes. Includes the use of at least 1, 2, 4, 6 or 8 of such nucleic acids or probes. The present invention includes detection of chromosomal interactions using any of the primers or primer pairs listed in Table 2 or 7, or using variants of these primers described herein (including primer sequences). Or a sequence containing a fragment of the primer sequence and / or a homologue).

「プライマーペア」の相同性は、例えば、２つの配列を単一の配列と見なすことで（２つの配列が連結されているかのように）計算することができ、その後に単一配列として再度考慮される別のプライマーペアと比較することができる。 The homology of a "primer pair " can be calculated, for example, by considering the two sequences as a single sequence (as if the two sequences were concatenated) and then reconsidered as a single sequence. Can be compared with another primer pair.

Claims

A process for detecting the state of a chromosome that indicates a disease subgroup in a population, including detecting whether or not a chromosomal interaction related to the state of the chromosome is present or absent within a defined region of the genome. The disease subgroup is the amyotrophic lateral sclerosis (ALS) subgroup and at least 4 represented by any probe or primer pair shown in Tables 1 , 5, 10 or 11. The process by which chromosomal interactions are classified.

The process of claim 1, which is performed to diagnose ALS or determine the prognosis of ALS.

Specific combinations of chromosomal interactions that are classified
(I) Table 1 or includes all chromosomal interactions are represented by probes in Table 5; or (ii) Table 1 or even 5, 6 or 7 chromosomes interact with less represented by Table 5 of the probe also no less that represented by or (iv) in Table 10 of the probe; where or (iii) Table 10 or any includes all chromosomal interactions are represented by probes or primer pairs as indicated in Table 11; comprising 5, 6 or 7 including a chromosome interaction
請Motomeko 1 or 2 process described.

Chromosome interaction ,
- by detecting the presence or absence of DNA loops at the site of chromosomal interactions, and / or - by detecting the presence or absence of the distal region of chromosome con chromosomes collected in conformation, and / or -The sequences generated during the classification are classified by detecting the presence of a ligated nucleic acid containing two regions, each corresponding to a region of the chromosome that is collected in a chromosomal interaction, where it is ligated. Detection of the nucleic acid is preferably (i) using a probe having at least 70% identity to any of the specific probe sequences listed in Table 1 or Table 5 and / or (ii) Table 2 or A primer pair having at least 70% identity with any of the primer pairs in Table 7 is used and / or
-The process according to any one of claims 1-3, wherein the process is performed to select an individual for medical treatment.

The process according to any one of claims 1-4 at least 5-9 different chromosomes interactions are classified.

A process for detecting the state of a chromosome that indicates a disease subgroup in a population, including detecting whether or not a chromosomal interaction related to the state of the chromosome is present or absent within a defined region of the genome. A process in which the disease subgroup is the Huntington's disease subgroup and at least four chromosomal interactions represented by any of the probes shown in Table 12 are classified .

6. The process of claim 6, which is performed to diagnose Huntington's disease or to determine the prognosis of Huntington's disease.

Specific combinations of chromosomal interactions that are classified
Includes all chromosomal interactions are represented by (i) Table 12 of the probe; or (ii) 5 to as little as represented by the 12 probe table, 6 or 7 including chromosomal interactions
請Motomeko 6 or 7 process according.

Chromosome interaction ,
- by detecting the presence or absence of DNA loops at the site of chromosomal interactions, and / or - by detecting the presence or absence of the distal region of chromosome con chromosomes collected in conformation, and / or -The sequences generated during the classification are classified by detecting the presence of a ligated nucleic acid containing two regions, each corresponding to a region of the chromosome that is collected in a chromosomal interaction, where it is ligated. Detection of the nucleic acid is preferably (i) using a probe having at least 70% identity to any of the specific probe sequences listed in Table 12 and / or (ii) any of Table 12. A primer pair having at least 70% identity with the primer pair is used and / or
- process according to any one of <br/> claims 6-8 carried out in order to select the individual for medical treatment process.

The process according to any one of claims 6-9 at least 5-9 different chromosomes interaction is classified.

Classification or detection involves specific detection of the ligation product by quantitative PCR (qPCR) using primers capable of amplifying the ligation product and a probe that binds to the ligation site during the PCR reaction, with the probes assembled in a chromosomal interaction. The probe contains a sequence complementary to the sequence derived from each chromosomal region, preferably the probe.
An oligonucleotide that specifically binds to the ligation product, and / or a fluorophore that is covalently attached to the 5'end of the oligonucleotide, and / or a quencher that is covalently attached to the 3'end of the oligonucleotide, and optionally.
The fluorophore is selected from HEX, Texas Red and FAM; and / or any one of claims 1-10 , wherein the probe comprises a nucleic acid sequence of 10-40 nucleotides in length, preferably 20-30 nucleotides in length. process as claimed in.